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Comment by Dr. Krishna Kumari Challa on August 14, 2024 at 8:17am

Significant link found between heme iron, found in red meat and other animal products, and type 2 diabetes risk

Higher intake of heme iron, the type found in red meat and other animal products—as opposed to non-heme iron, found mostly in plant-based foods—was associated with a higher risk of developing type 2 diabetes (T2D) in a new study  by researchers. While the link between heme iron and T2D has been reported previously, the study's findings more clearly establish and explain the link.

The researchers assessed the link between iron and T2D using 36 years of dietary reports from 206,615 adults enrolled in the Nurses' Health Studies I and II and the Health Professionals Follow-up Study. They examined participants' intake of various forms of iron—total, heme, non-heme, dietary (from foods), and supplemental (from supplements)—and their T2D status, controlling for other health and lifestyle factors.

The researchers also analyzed the biological mechanisms underpinning heme iron's relationship to T2D among smaller subsets of the participants. They looked at 37,544 participants' plasma metabolic biomarkers, including those related to insulin levels, blood sugar, blood lipids, inflammation, and two biomarkers of iron metabolism. They then looked at 9,024 participants' metabolomic profiles—plasma levels of small-molecule metabolites, which are substances derived from bodily processes such as breaking down food or chemicals.

The study found a significant association between higher heme iron intake and T2D risk. Participants in the highest intake group had a 26% higher risk of developing T2D than those in the lowest intake group. In addition, the researchers found that heme iron accounted for more than half of the T2D risk associated with unprocessed red meat and a moderate proportion of the risk for several T2D-related dietary patterns. In line with previous studies, the researchers found no significant associations between intakes of non-heme iron from diet or supplements and risk of T2D.

The study also found that higher heme iron intake was associated with blood metabolic biomarkers associated with T2D. A higher heme iron intake was associated with higher levels of biomarkers such as C-peptide, triglycerides, C-reactive protein, leptin, and markers of iron overload, as well as lower levels of beneficial biomarkers like HDL cholesterol and adiponectin.

The researchers also identified a dozen blood metabolites—including L-valine, L-lysine, uric acid, and several lipid metabolites—that may play a role in the link between heme iron intake and TD2 risk. These metabolites have been previously associated with risk of T2D.

But  the findings—based on a study population that was mostly white—must be replicated in other racial and ethnic groups to get established.

Integration of epidemiological and blood biomarker analysis links heme iron intake to increased type 2 diabetes risk, Nature Metabolism (2024). DOI: 10.1038/s42255-024-01109-5

On a population level, the study findings carry important implications for dietary guidelines and public health strategies to reduce rates of diabetes, according to the researchers. In particular, the findings raise concerns about the addition of heme to plant-based meat alternatives to enhance their meaty flavor and appearance. These products are gaining in popularity, but health effects warrant further investigation.

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 11:14am

Excessive heat can affect your mental health

While extreme heat can cause physical harm, it can also wreak havoc with your mental health.

Sizzling temperatures can make anyone irritable, but it can be far worse for some, especially those with mental health conditions. Excessive heat can trigger feelings of anger, irritability, aggression, discomfort, stress and fatigue because of its impact on serotonin, the neurotransmitter that regulates your sleep, mood and behaviours.

The most vulnerable groups include people with preexisting mental health conditions and people who abuse alcohol or other drugs.

All mental illnesses increase with heat because it results in more fatigue, irritability and anxiety, and it can exacerbate depressive episodes.

What are the signs of impending trouble? They tend to start with irritability, decreased motivation, aggressive behavior and sometimes mental fogging. In worse cases, confusion and disorientation occur.

If you take medications, consult with your provider because some medications for mental health, such as lithium for bipolar patients, don't pair well with heat. Lithium goes through the kidney, so sweating can have an impact on the levels of the medication in your body.

Droughts and extreme changes in temperature can also increase levels of pollutants and allergens as air quality worsens. That can exacerbate mental health issues like depression, anxiety or PTSD. Some studies show that exposure to any natural climate disaster can raise the risk of depression by more than 30%, anxiety by 70% and both by over 87%.

If you feel affected by severe heat, call your doctor or mental health specialist.

https://www.apa.org/monitor/2024/06/heat-affects-mental-health

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 11:08am

Brain biomarker in blood sample predicts stroke, researchers demonstrate

Researchers  have demonstrated that a simple blood test that reflects brain health can predict which people are most at risk of suffering a stroke. The discovery could contribute to more individualized treatment of patients with atrial fibrillation. The study has been published in the journal Circulation.

Atrial fibrillation is the most frequent cardiac arrhythmia, affecting around a third of all people at some point in their life. Atrial fibrillation is a common cause of stroke, since the cardiac arrhythmia increases the risk of blood clots forming in the heart's atria. Many people with atrial fibrillation therefore receive anticoagulation treatment with a view to preventing stroke.

However, since anticoagulation treatment leads to an increased risk of serious hemorrhages, only people with a moderate or high risk of experiencing a stroke receive this treatment, instead of all people with atrial fibrillation. This makes it important to be able to identify, with as high a degree of precision as possible, the individuals who will benefit from anticoagulation treatment.

The researchers have now analyzed the substance neurofilament, a protein that is released from the brain in cases of injurious strain and hypoxia, in blood samples from more than 3,000 people with atrial fibrillation. The researchers then followed these people for an average of one and a half years. The individuals with the highest neurofilament levels in their blood had the highest risk of suffering a stroke. The risk of stroke among the quarter with the highest neurofilament levels was more than three times as high as for those with the lowest levels.

As the risk of suffering a stroke determines which type of treatment is appropriate, this can help to increase the precision in the selection of treatment.

When the researchers then combined neurofilament with ordinary cardiac blood samples from the same individuals, this further increased the ability to predict stroke.

Julia Aulin et al, Neurofilament Light Chain and Risk of Stroke in Patients With Atrial Fibrillation, Circulation (2024). DOI: 10.1161/CIRCULATIONAHA.124.069440

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:39am

Pre-surgical antibody treatment might prevent heart transplant rejection

A new study from scientists  suggests there may be a way to further protect transplanted hearts from rejection by preparing the donor organ and the recipient with an anti-inflammatory antibody treatment before surgery occurs.

The findings, published online in the Proceedings of the National Academy of Sciences , focus on blocking an innate immune response that normally occurs in response to microbial infections. The same response has been shown to drive dangerous inflammation in transplanted hearts.

In the new study—in mice—transplanted hearts functioned for longer periods when the organ recipients also received the novel antibody treatment. Now the first of a complex series of steps has begun to determine whether a similar approach can be safely performed for human heart transplants.

The anti-rejection regimens currently in use are broad immunosuppressive agents that make the patients susceptible to infections. By using specific antibodies, scientists think they can just block the inflammation that leads to rejection but leave anti-microbial immunity intact.

 Pasare, Chandrashekhar, Alloreactive memory CD4 T cells promote transplant rejection by engaging DCs to induce innate inflammation and CD8 T cell priming, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2401658121

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:36am

Researchers found that with visual experience, feedback provides more contextual and novel information, enhancing the ability of V1 cells to sample information from a broader area of the visual scene.

This effect depended on the origin within the higher visual area: feedback projections from deeper layers were more likely to convey surrounding information compared to those from superficial layers.

Moreover, the team discovered that in normally-reared mice, deep-layer feedback inputs to V1 become organized according to the patterns they "prefer" to see, such as vertical or horizontal lines. For instance, inputs that prefer vertical lines avoid sending surrounding information to areas located along the vertical direction. In contrast, they found no such bias in connectivity in dark-reared mice.

This suggests that visual experience plays a crucial role in fine-tuning feedback connections and shaping the spatial information transmitted from higher to lower visual areas.
Researchers developed a computational model that shows how experience leads to a selection process, reducing connections between feedback and V1 cells whose representations overlap too much. This minimizes redundancy, allowing V1 cells to integrate a more diverse range of feedback.
Perhaps counter-intuitively, the brain might encode learned knowledge by connecting cells that represent unrelated concepts, and that are less likely to be activated together based on real-world patterns. This could be an energy-efficient way to store information, so that when encountering a novel stimulus, like a pink elephant, the brain's preconfigured wiring maximizes activation, enhancing detection and updating predictions about the world.

Identifying this brain interface where prior knowledge combines with new sensory information could be valuable for developing interventions in cases where this integration process malfunctions.

Visual experience reduces the spatial redundancy between cortical feedback inputs and primary visual cortex neurons., Neuron (2024). DOI: 10.1016/j.neuron.2024.07.009. www.cell.com/neuron/fulltext/S0896-6273(24)00531-2

Part 3

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Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:32am

The brain's visual system consists of a network of areas that work together, with lower areas handling simple details (e.g. small regions of space, colors, edges) and higher areas representing more complex concepts (e.g. larger regions of space, animals, faces).

Cells in higher areas send "feedback" connections to lower areas, putting them in a position to learn and embed real-world relationships shaped by experience.

For instance, cells encoding an "elephant" might send feedback to cells processing features like "gray," "big" and "heavy." The researchers therefore set about investigating how visual experience influences the organization of these feedback projections, whose functional role remains largely unknown.
Researchers examined the effects of visual experience on feedback projections to a lower visual area called V1 in mice. They raised two groups of mice differently: one in a normal environment with regular light exposure, and the other in darkness. They then observed how the feedback connections, and cells they target in V1, responded to different regions of the visual field.

In mice raised in darkness, the feedback connections and V1 cells directly below them both represented the same areas of visual space. It 's amazing to see how well the spatial representations of higher and lower areas matched up in the dark-reared mice. This suggests that the brain has an inherent, genetic blueprint for organizing these spatially aligned connections, independent of visual input. However, in normally-reared mice, these connections were less precisely matched, and more feedback inputs conveyed information from surrounding areas of the visual field.
Part 2

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:29am

How experience shapes neural connectivity in the brain

Our brain interprets visual information by combining what we see with what we already know. A study published in the journal Neuron, by researchers  reveals a mechanism for learning and storing this existing knowledge about the world.

They found that neurons are wired to connect seemingly unrelated concepts. This wiring may be crucial for enhancing the brain's ability to predict what we see based on past experiences, and brings us a step closer to understanding how this process goes awry in mental health disorders.

How do we learn to make sense of our environment? Over time, our brain builds a hierarchy of knowledge, with higher-order concepts linked to the lower-order features that comprise them.

This interconnected framework shapes our expectations and perception of the world, allowing us to identify what we see based on context and experience.

Part 1

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:25am

Rat poison is moving up through food chains, threatening carnivores around the world

Rats thrive around humans, for good reason: They feed off crops and garbage and readily adapt to many settings, from farms to the world's largest cities. To control them, people often resort to poisons. But chemicals that kill rats can also harm other animals.

The most commonly used poisons are called anticoagulant rodenticides. They work by interfering with blood clotting in animals that consume them. These enticingly flavored bait blocks are placed outside of buildings, in small black boxes that only rats and mice can enter. But the poison remains in the rodents' bodies, threatening larger animals that prey on them.

Researchers detected rodenticides in about one-third of the animals in these analyses, including bobcats, foxes and weasels. They directly linked the poisons to the deaths of one-third of the deceased animals—typically, by finding the chemicals in the animals' liver tissues.

When wild animals consume rat poison—typically, by eating a poisoned rat—the effects may include internal bleeding and lesions, lethargy and a reduced immune response, which can make them more susceptible to other diseases. In many cases the animal will die. Sometimes these deaths occur at scales large enough to reduce local predator populations.

 M. P. Keating et al, Global review of anticoagulant rodenticide exposure in wild mammalian carnivores, Animal Conservation (2024). DOI: 10.1111/acv.12947

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:10am

Toxoplasma parasites infect all animals, including humans. Infection can occur in multiple ways, including ingesting spores released in the stool of infected cats or consuming contaminated meat or water. Toxoplasmosis in otherwise healthy people produces only mild symptoms but can be serious in immunocompromised people and to gestating fetusus.

Unlike most pathogens, Toxoplasma can cross the blood-brain barrier and invade brain cells. Once inside neurons, the parasite releases a suite of proteins that alter gene expression in its host, which may be a factor in the behavioral changes it causes in infected animals and people.
In a new study, a global team of researchers hijacked the system Toxoplasma uses to secrete proteins into its host cell. The team genetically engineered Toxoplasma to make a hybrid protein, fusing one of its secreted proteins to a protein called MeCP2, which regulates gene activity in the brain—in effect, giving the MeCP2 a piggyback ride into neurons. Researchers found that the parasites secreted the MeCP2 protein hybrid into neurons grown in a petri dish as well as in the brains of infected mice.

A genetic deficiency in MECP2 causes a rare brain development disorder called Rett syndrome. Gene therapy trials using viruses to deliver the MeCP2 protein to treat Rett syndrome are underway. If Toxoplasma can deliver a form of MeCP2 protein into brain cells, it may provide another option to treat this currently incurable condition. It also may offer another treatment option for other neurological problems that arise from errant proteins, such as Alzheimer's and Parkinson's disease.
The road from laboratory bench to bedside is long and filled with obstacles, so don't expect to see engineered Toxoplasma in the clinic anytime soon.

The obvious complication in using Toxoplasma for medical purposes is that it can produce a serious, lifelong infection that is currently incurable. Infecting someone with Toxoplasma can damage critical organ systems, including the brain, eyes and heart.

However, up to one-third of people worldwide currently carry Toxoplasma in their brain, apparently without incident. Emerging studies have correlated infection with increased risk of schizophrenia, rage disorder and recklessness, hinting that this quiet infection may be predisposing some people to serious neurological problems.

The widespread prevalence of Toxoplasma infections may also be another complication, as it disqualifies many people from using it for treatment. Since the billions of people who already carry the parasite have developed immunity against future infection, therapeutic forms of Toxoplasma would be rapidly destroyed by their immune systems once injected.

In some cases, the benefits of using Toxoplasma as a drug delivery system may outweigh the risks. Engineering benign forms of this parasite could produce the proteins patients need without harming the organ—the brain—that defines who we are.

https://www.nature.com/articles/s41564-024-01750-6

Part 2

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Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:08am

A common parasite could deliver drugs to the brain—how scientists are turning Toxoplasma gondii from foe into friend

Parasites take an enormous toll on human and veterinary health. But researchers may have found a way for patients with brain disorders and a common brain parasite to become frenemies.

A new study published in Nature Microbiology has pioneered the use of a single-celled parasite, Toxoplasma gondii, to inject therapeutic proteins into brain cells. The brain is very picky about what it lets in, including many drugs, which limits treatment options for neurological conditions.

Preventing and treating disease by co-opting the very microbes that threaten us has a history that long predates germ theory. Vaccines are a good example. 

The concept of inoculation has yielded a plethora of vaccines that have saved countless lives.

Viruses, bacteria and parasites have also evolved many tricks to penetrate organs such as the brain and could be retooled to deliver drugs into the body. Such uses could include viruses for gene therapy and intestinal bacteria to treat a gut infection known as C. diff.

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